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    The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided?
    (2020) Kaplan, Muhammet Ali; Araz, Murat; Artaç, Mehmet; Sezgin, Yasin; Eryılmaz, Melek Karakurt; Karaağaç, Mustafa
    Objectives: Pazopanib is an orally administered drug and has approval for the treatment of advanced Soft TissueSarcomas (aSTS). The absorption of pazopanib is pH-dependent. Acid-Reducing drugs such as proton pump inhibitors(PPI) may reduce the bioavailability of pazopanib. The primary purpose of this study was to assess whether the use ofconcomitant PPI and pazopanib had negative effects on survival outcomes.Methods: In this retrospective cross-sectional study, age ?18 years, having histologically proven STS, receiving pazopanibat least one day, and availability of information about the use of PPI during pazopanib treatment were the inclusioncriteria. Patients with adipocytic sarcoma were excluded.Results: A total of 46 eligible patients were assessed in this study. Thirty-one patients used concomitant PPI andpazopanib, 17 of them frequently used PPI, and the others occasionally. Fifteen patients never used concomitant PPI andpazopanib. The median progression-free survival (PFS) was 2.76 months, and the median overall survival (OS) was7.39?months for patients who never used concomitant PPI and pazopanib. Also, the median PFS was 5.22 months, and themedian OS was 14.52?months for patients who used concomitant PPI and pazopanib. In univariate analysis; usingconcomitant PPI (p=0.049) and primarily uterine located tumors (p=0.038) were significant parameters for PFS. Inmultivariate logistic regression analysis; both of using concomitant PPI (Wald=6.02; p=0.014) and primarily uterinelocated tumors (Wald=5.69; p=0.017) retained their association with longer PFS. No parameter was significant for OS.Conclusions: We showed that the use of concomitant PPI and pazopanib was associated with improved PFS. These resultsmay help guide clinicians and researchers for allowing patients co-administrating PPI and pazopanib, especially whentreating or investigating patients with dyspeptic symptoms.
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    Öğe
    Where should enzalutamide be in the metastatic Castration Resistant Prostate Cancer (mCRPC): A multi-center study
    (Kare Publishing, 2023) Koca, Sinan; Ökten, İlker Nihat; Beşiroğlu, Mehmet; Telli, Tuğba Akın; Demirci, Ayşe; Karaağaç, Mustafa; Oruç, Zeynep
    Objectives: Enzalutamide(ENZ) is an effective hormonal treatment modality in mCRPC. It can be used before or after docetaxel(DTX) in this setting. Herein, we aimed to show the efficacy of ENZ before or after DTX use and the factors predicting the efficacy. Methods: We retrospectively collected the data of 320 patients from 12 centers who were treated with ENZ in mCRPC. The initial stage, age, line of treatment, serum prostate-specific antigen (PSA) levels before ENZ treatment and at nadir, site of metastasis, gleason score were evaluated. Results: Median age of 320 patients were 69. At a median follow-up of 56 months, 271/320 (84.7%) disease progression and 230/320(71.9%) death had been observed. Median PFS was 11(8.9-13)) and median OS was 25(22.1-27.8) months in all patients group. Median PFS was 10(7.4-12.5) months, 11(8-13.9) months in pre-DTX and post-DTX groups respectively. Median OS was higher in the post-DTX group than the pre-DTX group (28(25.7-30.2) vs 19(15.0-22.9-46.6) (p:0.000). Gleason score≥8 (HR 0.59, 95%CI 0.46-0.77, p=0.00), presence of non-visceral metastasis (HR 0.72, 95%CI 0.53-0.97, p=0.031), initial PSA value<43(median) (HR 0.70, 95%CI 0.54-0.91, p=0.009), PSA at nadir <2 (HR 0.61, 95%CI 0.44-0.85, p=0.004), >50% decline in PSA (HR 0.27, 95%CI 0.19-0.36, p=0.000) significantly predicted ENZ response regarding rPFS. Conclusion: ENZ has shown equal efficacy before and after DTX treatment in mCRPC regarding rPFS. But OS rate was significantly better in the pre-DTX group. Therefore, we recommend starting with DTX in patients who can tolerate chemotherapy in mCRPC setting.